Using morphologic techniques, this proposal addresses itself to the elucidation of certain structural, immunologic and virologic events occurring during selected chronic degenerative conditions of the human central nervous system. The studies pertain mostly to the etiology of multiple sclerosis (MS), the paradigm of the human demyelinating diseases, and subacute sclerosing panencephalitis (SSPE), a degenerative condition of young adolescents, caused by a defective measles virus. Series of experiments involving cultures of organized CNS and PNS tissue and parallel animal systems will attempt to dissect possible immunologic factors operative during autoimmune demyelination. Cultures will be exposed to sera and cells from animals inoculated with whole brain material, sensitized cells, myelin basic protein or purified preparations of oligodendroglial cells. Other cultures will be tested with sera and cells from MS patients at different stages of the disease. Immunological tagging experiments will be performed on the cultures to localize the possible sites of attachment of these factors in vitro. Virologic studies will continue to examine measles virus and several strains of SSPE virus in vivo and in vitro in terms of virus-host tissue relationships, neurovirulence, variation in viral assembly and virus replication. A recently developed immunoperoxidase system will be utilized on this in vitro system and cultures will be tested simulataneously for localization of measles virus antigen with similarly fixed fresh frozen CNS tissue from cases of human SSPE and MS tissue. Ultrastructural analysis of lesions from MS and animals with chronic experimental allergic encephalomyelitis will be continued. The combination of the above in vivo and in vitro experiments might shed new light on the etiology of a number of chronic degenerative conditions of the human CNS, particularly those in which myelin is selectively involved, and the interaction of immunologic and virologic factors in the pathogenesis of lesions.